Nutr Cancer., 2018, Oct 30:1-14. doi: 10.1080/01635581.2018.1516789.

Effect of Dietary Flaxseed Intake on Circulating Sex Hormone Levels among Postmenopausal Women: A Randomized Controlled Intervention Trial.

Chang VC, Cotterchio M, Boucher BA, et al.

Lignan intake, and its richest food source, flaxseed, have been associated with reduced breast cancer risk. Endogenous sex hormones, such as estrogens, play a role in breast cancer development, and lignans may alter these sex hormone levels. To assess the effect of flaxseed on circulating sex hormones, a randomized controlled trial was conducted among 99 postmenopausal women in Toronto, Canada. The intervention arm consumed 2 tablespoons (15 g) of ground flaxseed daily for 7 weeks; the control arm maintained usual diet. Baseline and week 7 concentrations of 14 serum sex hormones were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay, and serum enterolignans (lignan biomarker) using LC-MS/MS. Intervention effects on sex hormone levels were assessed using analysis of covariance. Serum enterolignans increased among the flaxseed arm (+516%). Women consuming flaxseed (vs. controls) had increased serum 2-hydroxyestrone [treatment effect ratio (TER) = 1.54; 95% CI: 1.18-2.00] and 2:16α-hydroxyestrone ratio (TER =1.54; 95% CI: 1.15-2.06); effects on other hormones were not statistically significant. Within the flaxseed arm, change in enterolignan level was positively correlated with changes in 2-hydroxyestrone and 2:16α-hydroxyestrone ratio, and negatively with prolactin. Findings suggest flaxseed affects certain circulating sex hormone levels with possible implications for future breast cancer prevention research.

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Despite biological plausibility and evidence from observational studies, only a few small intervention trials have assessed the effect of flaxseed on endogenous sex hormone levels among postmenopausal women. This randomized controlled intervention study was conducted among postmenopausal women to investigate the effect of daily flaxseed intake on circulating serum levels of a wide spectrum of sex hormones and their metabolites. In addition, the effect of flaxseed on circulating enterolignan levels, as well as correlations between changes in enterolignan levels and changes in sex hormone levels, were assessed. This randomized intervention trial among postmenopausal women found that intake of ground flaxseed daily for 7 weeks significantly increased circulating 2-hydroxyestrone level and the 2:16a-hydroxyestrone ratio; however, no statistically significant effects were seen for other sex hormones assessed. Flaxseed consumption substantially increased circulating enterolignans, which were in turn positively correlated with changes in 2-hydroxyestrone and 2:16a-hydroxyestrone ratio, supporting the hypothesis that effects of flaxseed on estrogen metabolism may be mediated through mechanisms involving lignans. The findings add to the literature suggesting flaxseed intake may alter estrogen profiles of importance for breast cancer prevention, as these estrogen profiles have been shown to be associated with breast cancer risk. In conclusion, the findings suggest that dietary flaxseed may modulate estrogen levels and metabolism among postmenopausal women, particularly by increasing circulating 2-hydroxyestrone levels, and consequently, improving the 2:16a-hydroxyestrone ratio.